stabilization shellac

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European Journal of Pharmaceutics and Biopharmaceutics 67 (2007) 690–698

Research paper

Enhanced enteric properties and stability of shellac filmsthrough composite salts formation

Sontaya Limmatvapirat a,*, Chutima Limmatvapirat b, Satit Puttipipatkhachorn c,Jurairat Nuntanid a, Manee Luangtana-anan a

a Department of Pharmaceutical Technology, Silpakorn University, Nakhon Pathom, Thailandb Department of Pharmaceutical Chemistry, Silpakorn University, Nakhon Pathom, Thailand

c Department of Manufacturing Pharmacy, Mahidol University, Bangkok, Thailand

Received 25 January 2007; accepted in revised form 11 April 2007Available online 20 April 2007

Abstract

The objective of this study was to improve the properties of shellac by composite salts formation. The shellac samples were preparedin various salt forms by dissolving them with 2-amino-2-methyl-1-propanol (AMP) and ammonium hydroxide (AMN) at various ratiosof AMP:AMN. The results demonstrated that aqueous solubility of the shellac salts was improved as the ratio of AMP:AMN increased.The absorbance ratio of the FTIR peaks assigned to C@O stretching of carboxylate and carboxylic acid (ABS1556/ABS1716) wasincreased with the increase of the AMP fraction, suggesting that the solubility enhancement was due to more ionization of AMP salts.Moisture adsorption studies indicated that shellac salts were more hygroscopic as AMP content increased. After storage at 40 �C, 75%RH, the acid value and insoluble solid of AMP salts were relatively constant even after storage of up to 180 days, suggesting that AMPshould protect polymerization. The ABS1556/ABS1716 values of the shellac salts were rapidly decreased after storage, especially for thoseconsisting of a high percentage of AMN. Thus, AMP should bind much tighter at the carboxylate binding site as compared with AMN,resulting in more solubility and stability. In conclusion, optimized shellac properties could be easily accomplished by composite saltsformation.� 2007 Elsevier B.V. All rights reserved.

Keywords: Shellac; Salt; Enteric; Film; Stability; Ammonia; 2-Amino-2-methyl-1-propanol

1. Introduction

Shellac is a purified resinous secretion of lac insects,Laccifer Lacca, which are mostly cultivated in host trees inIndia and Thailand. The shellac is widely used in the foodindustry, to some extent still in the pharmaceutical industryand a market of growing interest in nutritional supplement,health supplement, and nutriceuticals [1]. In the pharmaceu-tical industry, shellac has been used for moisture protectionand glossing, while the use for enteric coating of pharmaceu-tical products has greatly declined [2]. Severe problems

0939-6411/$ - see front matter � 2007 Elsevier B.V. All rights reserved.

doi:10.1016/j.ejpb.2007.04.008

* Corresponding author. Department of Pharmaceutical Technology,Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000,Thailand. Tel.: +66 34255800; fax: +66 34255801.

E-mail address: [email protected] (S. Limmatvapirat).

associated with enteric properties are low solubility at thepH of the intestine and lesser stability of shellac as comparedto synthetic and semi-synthetic enteric polymers, e.g., poly-acrylates and cellulose derivatives [3]. The shellac possessesa high pKa between 6.9 and 7.5 and begins to dissolve atpH 7.0. However, the pH in the proximal region of the smallintestine is between 3.8 and 6.9 and the failure of shellaccoated tablets or capsules to disintegrate at these pH mediais still a major problem [2,4]. During many years, severalattempts have been made to clarify the problem. Pearnchobet al. developed a faster disintegrated shellac coated capsuleby adding organic acids, e.g., sorbic acid and benzoic acid.The addition of organic acids decreased the disintegrationtime in phosphate buffer (pH 6.8) while the behavior in0.1 N hydrochloric acid was unchanged [5]. The hydrolysisprocess was also used as a method for improving the

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S. Limmatvapirat et al. / European Journal of Pharmaceutics and Biopharmaceutics 67 (2007) 690–698 691

solubility of shellac. The partially hydrolyzed shellac showedgreater solubility and dissolution, especially at pH 7.0 andlower [6]. However, a stabilization method for shellac isnot completely developed.

As shown in Fig. 1, shellac is composed of polyestersand single esters that contain a large amount of hydroxyland carboxylic acid. The polymerization can occur by theesterification among the functional groups and was thecause of instability [7]. Since the polymerization occurredvia a carboxyl group, the protection at the carboxylic acidshould be a possible means for improving the stability ofshellac. Specht et al. demonstrated that application of shel-lac from an aqueous solution of alkali salts showed betterstability than the application from ethanolic solution [8].Similar results were observed by our group. The ammo-nium salt of shellac demonstrated better stability and solu-bility, as compared with shellac in free acid form [9].However, the stability of ammonium salts was decreasedafter storage at stress condition for a long period, especiallyunder the test condition of a tropical zone (40 �C, 75% RH)for more than 3 months. The loss of ammonium ion fromthe carboxylic group might be a possible explanation thatstill needed to be investigated. In addition, another saltforming agent, especially one more tightly bound to thecarboxylic acid, should be examined and the mechanismof the stabilization process should be further clarified.

The aim of the present study was to evaluate the effect ofsalt forming agents on enteric properties and stability ofshellac. Ammonium hydroxide (AMN), 2-amino-2-methyl-1-propanol (AMP) and the combination of bothbases were selected as the salt forming agents in this study.The shellac samples, in acid form and various salt forms,were prepared and comparatively evaluated.

2. Materials and methods

2.1. Materials

Shellac was purchased from Thananchai Part., Ltd.(Bangkok, Thailand). Other reagents used were of analyti-cal grade and used as received.

R'

R

OO

(CH2)7

CHOH

CHOH

(CH2)5

CH2OH

O

O

R'

R

OO

(CH2)7

CH

CHOH

(CH2)5

CH2OH

O

O

polyesters

Fig. 1. Chemical stru

2.2. Methods

2.2.1. Preparation of partially hydrolyzed shellac

Partially hydrolyzed shellac was prepared by a previ-ously described method [6]. Shellac (200 g) was dissolvedin 2% w/w sodium hydroxide solution (1800 g) and keptat 30 ± 1 �C for 8 min. The mixtures were then immedi-ately neutralized with 2 N sulfuric acid, washed with excesswater, and dried. The partially hydrolyzed shellac was keptin the refrigerator prior to use.

2.2.2. Preparation of shellac films in acid form and various

salts forms

Shellac films, in acid form and salt forms, were preparedusing the casting/solvent evaporation technique. For theacid form, the partially hydrolyzed shellac was dissolvedin ethanol overnight and then the final concentration wasadjusted to 12% w/w. The solution was poured onto apolytetrafluoroethylene (PTFE) plate and allowed to evap-orate at 50 �C for 2–3 h. The film was peeled off and stabi-lized at 25 �C, 75% RH prior to testing. In the case of saltforms, films of the 0:100 (100% AMN) salt, 100:0 (100%AMP) salt and 20:80, 40:60, and 80:20 AMP:AMN com-posite salts were prepared. The partially hydrolyzed shellacwas dispersed in water, then AMN, AMP or combinationsof these bases were added. The amounts of added baseswere calculated in accordance with the acid value of par-tially hydrolyzed shellac. The solutions were stirred over-night and then the cast films were prepared by the samemethod as described above, except that the drying timewas changed to 4–5 h.

2.2.3. Characterization of films

2.2.3.1. Film thickness. The film thickness (160 ± 30 lm)was measured at five points with a thickness gauge Mini-Test 600 (ElektroPhysik Dr. Steingroever GmbH & Co.KG, Germany).

2.2.3.2. Acid value and insoluble solid. Acid value (AV) wasdetermined by the acid–base titration method adapted fromthe United States Pharmacopeia [10]. An accurately

R'

R

OO

(CH2)7

CHOH

CHOH

(CH2)5

CH2OH

O

OH

R'

R

OO

(CH2)7

CH

CHOH

(CH2)5

CH2OH

O

OH

single esters

cture of shellac.

692 S. Limmatvapirat et al. / European Journal of Pharmaceutics and Biopharmaceutics 67 (2007) 690–698

weighted 3 g of finely ground shellac film was dissolved inethanol overnight and finally adjusted to the total weightof 39 g with ethanol. The solution was centrifuged and fil-tered through filter paper. The 26 g of filtrate (equivalentto 2 g of shellac) was titrated with 0.1 N sodium hydroxideVS. The end point was determined by pH meter instead ofusing color indicator due to the dark color of shellac. Theinsoluble solid on filter paper was washed with excess ethanoland dried at 70 �C until the dried weight was constant, andthen the percentage of insoluble solid was calculated.

2.2.3.3. Solubility. The solubility of the film was determinedby a method adapted from Wu et al. [11]. At first, the filmwas cut in a square of 1 cm · 1 cm and weighed. The filmwas then placed in each of six tubes of the basket of USPdisintegration apparatus which maintained the temperatureat 37 ± 2 �C. The simulated gastric fluid (SGF) was used asimmersion fluid for the first 2 h. After immersion in SGF,the film was transferred to buffer at various pH valuesfor the next 3 h. The resulting film was dried at 70 �C for12 h, and reweighed. The percentage of dissolved filmwas calculated from the percent weight loss of film.

In the case that the film was completely dissolved within3 h in buffer, the dissolution times were recorded.

2.2.3.4. Moisture adsorption. Moisture adsorption wasdetermined by placing shellac samples into a controlledhumidity environment at a constant temperature until equi-librium [12]. After drying samples until constant weight, thedried samples were placed into environments of various rel-ative humidities above salt solutions in desiccators. The rel-ative humidities were 11% RH (lithium chloride), 32% RH(magnesium chloride), 54% RH (sodium dichromate), 75%RH (sodium chloride), 85% RH (potassium chloride), and93% RH (potassium nitrate). The samples were equilibratedat each condition for 5–10 days at 25 ± 2 �C and then imme-diately weighed after removal from the desiccators. Theweight gain of the samples was recorded.

2.2.3.5. Mechanical properties. The mechanical propertiesof the shellac films were measured by a puncture test as pre-viously described [13]. A texture analyzer (TA.XT.plusTexture Analyzer, Stable Micro Systems, UK), equippedwith a spherical puncturing probe (diameter 5 mm), wasemployed. The film was placed in a holder with a cylindri-cal hole (r = 1.0 cm). The probe was driven through thefilm with a speed of 0.1 mm/s and force–displacementcurves were recorded through a 50 N load cell. The maxi-mum load and the maximum displacement of films weremeasured, and then converted to puncture strength, elon-gation at puncture and modulus at puncture. The parame-ters were calculated as follows [14]

Puncture strength ¼ F max

ACS

where Fmax is the maximum applied force, ACS the cross-sec-tional area of the edge of the film located in the path of the

cylindrical hole of the film holder, with ACS = 2rd, where r

is the radius of the hole and d is the thickness of the film

Elongation ð%Þ ¼ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffir2 þ d2

p� r

r� 100

where r is the radius of the film exposed in the cylindricalhole of the film holder and d represents the displacementof the probe from the point of contact to point of puncture.

Modulus at puncture ¼ Puncture strength

Elongation ð%Þ

2.2.3.6. Differential scanning calorimetry (DSC). Films ofshellac samples were dried over silica gel and pulverizedwith agate mortar. DSC curves of ground samples wererecorded using a differential scanning calorimeter (Sap-phire, Perkin Elmer, USA). Each sample (5–6 mg) wasaccurately weighed into an aluminum pan. The measure-ments were performed between 10 and 250 �C at a heatingrate of 10 �C/min. To determine the effect of pulverization,shellac samples were also directly casted into DSC pansand measured by the same condition.

2.2.3.7. Hot stage microscopy (HSM). All HSM photo-graphs were recorded using a light microscope (Olympus,BX50, Japan) equipped with hot stage controller (Collet,S516P, Japan). Finely ground shellac films were observedunder the microscope at a heating rate of 10 �C/min.Changes in the morphology of various salts were compar-atively evaluated as a function of temperature.

2.2.3.8. Fourier transformed infrared (FTIR) spectroscopy.

FTIR spectra of samples were recorded with a FTIR spec-trophotometer (Nicolet, Magna 750, USA) using the KBrdisc method. Each film was pulverized, gently trituratedwith KBr powder and then pressed using a hydraulic pressat a pressure of 5 tons. The KBr disc was placed in the sam-ple holder and scanned from 4000 to 400 cm�1 at a resolu-tion of 4 cm�1.

2.2.4. Stability study

The stability study was carried out under stress condi-tions of tropical areas. Shellac films were kept in a stabilitycabinet at 40 �C, 75% RH for 6 months. The films wereperiodically withdrawn and then characterized by themethods described above.

2.2.5. Statistical analysisData were expressed as means ± standard deviation

(SD). The statistical analysis was carried out using analysisof variance (ANOVA) at the 0.01 significance level.

3. Results and discussion

3.1. Physicochemical properties

The effects of salt forming agents (bases) on physico-chemical properties, including solubility, acid value and


insoluble solid, were determined. Shellac salts with variousratios of AMP:AMN at 0:100, 20:80, 40:60, 60:40, 80:20,and 100:0 were compared with the free acid form.

Fig. 2 demonstrates the percentage dissolved (bar chart)and dissolving time (line chart) of various shellac formsafter immersion in simulated gastric fluid for 2 h andtransferring to buffer at various pH values for 3 h.From our previous work [6], the pH solubility profile ofshellac was established. The results demonstrated that shel-lac was partially dissolved at pH 7.0 and completely dis-solved at pH 7.3 and higher. Therefore, we selected pH7.0 and pH 7.3 as representative pH values for the studyof percentage dissolved and dissolving time, respectively.The percentage dissolved of shellac salts was significantlyincreased while the dissolving time was significantlydecreased (p < 0.01), suggesting the enhancement of aque-ous solubility after salt formation. In addition, the percent-age dissolved was with increase of the AMP fraction, i.e.,percentage dissolved of 100:0 > 80:20 > 60:40 > 40:60 >20:80 > 0:100 AMP:AMN. The dissolving time was alsodecreased with increasing AMP content. Therefore, AMPsalt not only increased the percentage of dissolved shellacat lower pH but also increased the rate of dissolution athigher pH. The result suggested that AMP should be amore suitable salt forming agent for enhancing aqueoussolubility as compared to AMN.

The total number of carboxyl groups, expressed by acidvalue, controls the solubility of enteric polymers. In addi-tion, the ionization also affects the aqueous solubility. AspH increases, the acid–salt equilibrium shifts to the forma-tion of the ionized form with increasing aqueous solubility.Thus, the solubility of shellac is assumed to be controlledby 2 parameters, i.e., the total number of carboxyl groupsand the carboxylate/carboxylic acid ratio.

The acid value of shellac was increased as propagationof alkaline hydrolysis time. The increment of solubilitywas observed in partially hydrolyzed shellac [6]. To studythe extent of hydrolysis during film preparation by variousbases, the acid value of each salt form was determined.

0

20

40

60

80

100

acidform

0:100 20:80 40:60 60:40 80:20 100:0

AMP:AMN (%)

% d

isso

lved

0

20

40

60

80

100

Dis

solv

ing

tim

e (m

in)

% dissolveddissolving time

Fig. 2. Effect of salt formation on percentage dissolved at pH 7.0 anddissolving time at pH 7.3 of shellac films.

Acid values of acid form, 0:100, 20:80, 40:60, 60:40,80:20, and 100:0 AMP:AMN salts were 90, 97, 90, 92,91, 90, and 90, respectively. The acid values of all saltforms were not increased as compared with the acid form.The result suggested that alkaline hydrolysis did not obvi-ously occur during film preparation with both bases.Therefore, the improvement of aqueous solubility wasnot due to the increment of total number of carboxylgroups and should involve the increase of the carboxyl-ate/carboxylic acid ratio.

3.2. FTIR spectroscopy

FTIR spectroscopy was employed for monitoring theconversion of carboxylic acid to carboxylate. Fig. 3 illus-trates the FTIR spectra of shellac in acid form and varioussalt forms. The acid form showed a broad band peak in therange of 3600–3200 cm�1 with the maxima around3400 cm�1, which could be attributed as OAH stretching.The peak at 1716 cm�1 due to C@O stretching of the carbox-ylic acid (and also overlapped by that of an aldehyde orketone) was also observed. The 0:100 AMP:AMN saltshowed the new peaks at 1556 and 1385 cm�1 which wereassigned as asymmetric and symmetric C@O stretching ofcarboxylate, respectively, while the relative absorbance ofthe peak at 1716 cm�1 declined. The results suggested theconversion of carboxylic acid to carboxylate after salt forma-tion. The 100:0 AMP:AMN salt showed similar results anddemonstrated the more pronounced effect on carboxylateformation. The relative absorbance ratios of the FTIR peaksassigned to C@O stretching of carboxylate and carboxylicacid (ABS1556/ABS1716) were increased with an increase ofthe AMP fraction (100:0 > 80:20 > 60:40 > 40:60 >20:80 > 0:100 AMP:AMN). Thus, it was confirmed thathigher solubility of AMP salts was due to the increased ion-ization of shellac.

Ab

sorb

ance

Acid form0:10020:80

40:60

100:0

80:20

60:40

Wavenumber (cm-1)

4000 3000 2000 1500 1000 500

ig. 3. FTIR spectra of acid form and various salt forms (AMP:AMN) ofhellac.

Fs

0:100

20:80

40:60

100:0

80:20

60:40

30 50 70 90 110 130 150

Endo

ther

mic

Acid form

Temperature (°C)

Fig. 4. DSC curves of acid form and various salt forms (AMP:AMN) ofshellac.


Generally, ionization of acid depended on the basicity ofused bases. The pKa values of AMP and AMN were 9.69and 9.25, respectively [15]. The more basic AMP baseshould be a possible explanation for the increased ioniza-tion of shellac. However, the pKa value of AMP wasslightly higher than that of AMN, thus other factors mightalso affect the solubility of shellac salts. The AMP+ ionmight interact more strongly at the COO� binding site,as compared with NHþ4 . The detail of interaction will befurther discussed in the section on stability study.

0.0

5.0

10.0

15.0

20.0

25.0

0 25 50 75 100

Relative humidity (%)

Mo

situ

re u

pta

ke (

%)

100:0

80:20

60:40

40:60

20:80

0:100

acid form

Fig. 5. Moisture adsorption of acid form and various salt forms(AMP:AMN) of shellac.

3.3. Thermal analysis

To investigate the correlation between melting point andsolubility and also to further characterize shellac salts,thermal analysis was performed. Fig. 4 shows DSC curvesof shellac in acid form and various salt forms. The acidform indicated a clear endothermic peak at 58 �C, whilethe corresponding salt forms demonstrated a broad endo-thermic region in the range of 20–130 �C. The broad endo-thermic region tended to shift to the lower temperaturewith increasing percentage of AMP.

To clarify the unclear thermal behavior on DSC curves,we employed hot stage microscopy (HSM) for the study.The HSM photomicrograph of the acid form revealed thatthe endothermic peak of the acid form was due to melting,as shown by the liquid droplet formation after heating to60 �C. The 0:100 AMP:AMN salt did not clearly showthe fusion. The only partial melt at the surface wasobserved with even heating to more than 100 �C. Thebroad endothermic region in the DSC curve should bedue to water loss and partial melting (the moisture content

of shellac salts was about 5–6% w/w). The endothermicband due to loss of water should obscure the peak,assigned to melting. Similar results were observed for the20:80 AMP:AMN salt. The incomplete fusion, thoughmore obviously seen, was detected. However, the completefusion was observed in 40:60, 60:40, 80:20, and 100:0AMP:AMN salts. The samples were entirely melted at135, 115, 105, and 90 �C, respectively. The results suggestedthat the melting temperature decreased as the percentage ofAMP increased. The results also agreed with the work ofO’Conner and Corrigan. The study indicated the inverserelationship between melting point and solubility [16].Thus, the lower melting point of AMP salt should correlatewith the higher solubility as compared with the AMN salt.

3.4. Moisture adsorption study

Hygroscopicity is also an important parameter for selec-tion of a suitable salt form. Although the shellac possessedvery low water vapor permeability as compared with otherenteric polymers [3], the salt formation might affect thehygroscopicity. To study the effect of salt forming agentson hygroscopicity, moisture adsorption of the acid formand various salt forms of shellac was elucidated (Fig. 5).The acid form showed significantly lower moisture adsorp-tion as compared with the salt forms (p < 0.01). Moistureuptake of the acid form was less than 3%, even whenincreased to 93% RH while that of 100:0 AMP:AMN saltwas more than 20%. The higher fraction of AMP saltsshowed tendency to absorb more moisture, especially afterstorage above 75% RH. Since the hygroscopicity of saltswas dependent on their aqueous solubility [17], theincreased solubility of the AMP salt should be a possibleexplanation for more water adsorption as compared withthat of the AMN salt. In addition, a high fraction ofAMP should be avoided regarding hygroscopic concern.


3.5. Mechanical properties

Mechanical properties of shellac, including puncturestrength, elongation, and modulus at puncture, are shownin Fig. 6. The change of shellac from the acid form to0:100 AMP:AMN salt significantly increased (p < 0.01)the modulus of film (Fig. 6a). The high modulus resultedfrom the high puncture strength and the low percentageof elongation of 0:100 AMP:AMN (Fig. 6b). The datasuggested the hardness and brittleness of the film afterammonium salt formation. A similar change of mechani-cal properties was observed by using other enteric poly-mers, including cellulose acetate phthalate, celluloseacetate trimellitate and hydroxypropyl methylcellulosephthalate. Ammoniated enteric films showed somewhatmore brittleness than the acid form prepared from organicsolvent [18].

The flexibility of films was increased when the percent-age of AMP salt was increased, as observed by the incre-ment of percentage of elongation. The percentage ofelongation was increased 12 times after changing the ratioof AMP:AMN from 0:100 to 100:0. From the point of flex-ibility, AMP salts should be more suitable for film forma-tion than AMN salts. However, the puncture strength,which indicated the resistance to mechanical force duringcoating, had a tendency to decline. The puncture strengthsof 20:80, 40:60, 60:40, 80:20, and 100:0 AMP:AMNsalts were 9.8, 8.3, 6.6, 3.2, and 2.4 MPa, respectively.

0.0

2.0

4.0

6.0

8.0

10.0

12.0

acid form 0:100 20:80 40:60 60:40 80:20 100:0

AMP:AMN (%)

Pu

nct

ure

str

eng

th (

MP

a)

0.0

30.0

60.0

90.0

120.0

150.0

180.0

Elo

ng

atio

n (

%)

Puncture strength

Elongation

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

acid form 0:100 20:80 40:60 60:40 80:20 100:0

AMP:AMN (%)

Mo

du

lus

(MP

a)

a

b

Fig. 6. Mechanical properties of acid form and various salt forms(AMP:AMN) of shellac: (a) modulus at puncture, (b) puncture strengthand percentage of elongation.

Therefore, composite salts, especially in the ratio ofAMP:AMN from 20:80 to 60:40, should be more suitablethan pure ammonium or AMP salts, regarding theoptimized strength and strain of the film.

Generally, the addition of plasticizers increases per-centage of elongation, but often is accompanied by thereduction of strength and modulus. Various plasticizers,including triethyl citrate and polyethylene glycol, coulddecrease the glass transition point and change themechanical properties of shellac film [5,19]. However,the causes of modified mechanical properties of shellacsalts were considered to be different, as plasticizer freefilms were prepared. With regard to the moisture adsorp-tion study in Fig. 5, the moisture content was increasedwith increasing percentage of AMP. Therefore, it shouldbe possible that water could act as a plasticizer, resultingin more change of mechanical properties of AMP salts.Similar plasticization effects of water have been recog-nized [20]. Another possibility should relate to the interac-tion between salt forming agent and polymer chain ofshellac. Since AMP possessed an extra hydroxyl groupas comparing with AMN, the hydrogen bond might pro-mote the interaction between AMP and the polymerchain, resulting in more plasticization effect. The moreplasticization effect agreed with the lower melting temper-ature as increasing percentage of AMP.

3.6. Stability study

3.6.1. Effect of ageing on insoluble solid

Insoluble solid is one of the parameters that indicatethe stability of shellac. After storage, shellac was polymer-ized to form an insoluble solid which could not dissolvein ethanol. Fig. 7 demonstrates the percentage of insolu-ble solid of shellac in the acid form and various saltforms after storage. As expected, the percentage of insol-uble solid of acid form was immediately increased as

0

20

40

60

80

0 30 60 90 120 150 180

Storage time (days)

Inso

lub

le s

olid

(%

)

acid form

0:100

20:80

40:60

60:40

80:20

100:0

Fig. 7. Change of percentage of insoluble solid of acid form and varioussalt forms of shellac after storage at 40 �C, 75% RH for 6 months.


prolongation of storage time. The pronounced incrementof percentage of insoluble solid was observed after storagefor 15 days (p < 0.01). However, the percentage of insolu-ble solid of 0:100, 20:80, and 40:60 AMP:AMN salts wasincreased after storage for 60, 90 and 180 days, respec-tively. The 60:40, 80:20, and 100:0 AMP:AMN salts didnot show a clear increment of percentage of insolublesolid, even with storage of up to 6 months. These resultsindicated that the polymerization was protected due tosalt formation, and the more stabilization effect of AMPsalts over AMN salts was observed.

3.6.2. Effect of ageing on percentage dissolved of shellac films

at pH 7.0We also studied the stability of shellac films by moni-

toring the change of percentage dissolved at pH 7.0(Fig. 8). For 60:40, 80:20, and 100:0 AMP:AMN salts,the percentage of dissolved films was not changed withincreasing storage time. The result agreed well with thepercentage of insoluble solid, confirming that polymeriza-tion did not occur even with storage of up to 6 months.The percentage dissolved of 40:60 AMP:AMN salt wasrapidly decreased at the initial period and slightlydecreased after 30 days. Since the percentage of insolublesolid was not significantly changed (Fig. 7), the decreaseof percentage dissolved of 40:60 AMP:AMN salt shouldnot be involved with the polymerization. The conversionof carboxylate form to carboxylic acid after losing someAMN or AMP from the carboxylate binding site couldbe a possible reason for reduction of the percentage dis-solved. For 0:100 or 20:100 AMP:AMN salts, the percent-age dissolved was significantly decreased as increasingstorage time (p < 0.01). Both carboxylate conversion andpolymerization should be possible explanations for theresult. The conversion of carboxylate to carboxylic acidshould be a reason for decreasing of percentage dissolvedat the initial period. After carboxylate conversion, thepolymerization could then initiate, resulting in greaterdecrease of percentage of dissolved films after prolongedstorage.

0

20

40

60

80

100

0 30 60 90 120 150 180

Storage time (days)

% d

isso

lved

100:0

80:20

60:40

40:60

20:80

0:100

acid form

Fig. 8. Change of percentage dissolved at pH 7.0 of acid form and varioussalt forms of shellac after storage at 40 �C, 75% RH for 6 months.

3.6.3. Investigation of ageing mechanism by FTIR

spectroscopy

In order to investigate the increased stabilization effectof AMP over AMN, the FTIR spectra of all shellac saltswere comparatively evaluated for 6 months. The changesof ABS1556/ABS1716 (which represented the carboxylate/carboxylic acid ratio as discussed in Section 3.2) of allshellac salts are illustrated in Fig. 9. For 0:100 AMP:AMNsalt, the absorbance ratio was rapidly decreased afterstorage, however, for the 100:0 AMP:AMN salt, theabsorbance ratio was gradually decreased. After storagefor 6 months, the absorbance ratio of 100:0 AMP:AMNsalt was 7 times more than the 0:100 AMP:AMN salt.In addition, the slower decrease of the absorbance ratiowas observed with increasing the AMP fraction. Theresults suggested that AMP should interact muchstronger than AMN at the carboxylate binding site,and prevent the conversion of carboxylate to carboxylicacid.

Fig. 10 demonstrates the proposed diagram of salt for-mation and ageing mechanism of various forms of shellac.The acid form was rapidly polymerized by esterificationamong hydroxyl and carboxyl groups of polymer chainsof shellac after ageing, resulting in increasing of the per-centage of insoluble solid and lowering of the acid valueand aqueous solubility. However, the polymerizationcould be protected by salt formation with AMN orAMP. The carboxylic acid to carboxylate conversioncould increase the solubility and stabilize the shellac.AMP should more strongly interact with the carboxylate,resulting in more ionization, plasticization and stability ascompared to AMN. The increased interaction wasassumed to involve the hydrogen bond formation betweenhydroxyl groups of AMP and shellac. In addition, the ste-ric effect of the large molecular size of AMP might causethe polymer chains to separate from each other andreduce the possibility of esterification among polymerchains of shellac.

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 30 60 90 120 150 180

Storage time (days)

AB

S15

56/A

BS

1716

100:0

80:20

60:40

40:60

20:80

0:100

Fig. 9. Change of ABS1556/ABS1716 of various salt forms after storage at40 �C, 75% RH for 6 months.

Fig. 10. Proposed diagram of salt formation and ageing of various forms of shellac.


4. Conclusion

The improved enteric properties of the shellac films wereeasily achieved by AMP:AMN composite salts formation.The main disadvantages of AMN salt, including less solu-

bility and less stability, were compensated for by combina-tion with AMP salt, whereas the main disadvantages ofAMP, including high hygroscopicity and low film strength,were counterbalanced by combination with AMN salt. Theoptimum ratio of AMP:AMN should be in the range of


40:60–80:20 with regard to solubility, hygroscopicity,mechanical properties and stability of film.

Acknowledgements

This work was supported by the Thailand ResearchFund, the Commission on Higher Education, the ResearchInstitute of Silpakorn University and the Faculty of Phar-macy, Silpakorn University. The authors also would like tothank Mr. Vacharapon Rangnim for his technicalassistance.

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stabilization shellac

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